MiR-1 Suppresses Proliferation of Osteosarcoma Cells by Up-regulating p21 via PAX3

Abstract

Background/Aim: miRNA-1(miR-1) is downregulated in various cancer cells including osteosarcoma cells. This study was conducted to analyze the function of miR-1 in osteosarcoma cells. Materials and Methods: miR-1 expression in osteosarcoma cells was evaluated by qRT-PCR. Cell proliferation was evaluated after transfecting miR-1 by WST8 assay and FACS analysis, both in vitro and in vivo. Results: Overexpression of miR-1 suppressed cell proliferation and induced cell-cycle arrest in the G 0-G 1 phase by increasing p21 levels via a p53-independent pathway. Overexpression of miR-1 down-regulated PAX3, a potential p21-regulating gene. Moreover, knockdown of PAX3 suppressed cell proliferation by increasing p21 levels, and induced arrest at the G 0 /G 1 phase. Administration of miR-1 showed an in vivo antitumor effect. Conclusion: Overexpression of miR-1 suppressed cell proliferation and induced arrest in the G 0 /G 1 phase by increasing p21 levels via a p53-independent pathway through PAX3 suppression. These results indicate that miR-1 could be a therapeutic target for osteosarcoma. Osteosarcoma is a primary bone malignancy that usually occurs in the metaphyseal region of long bones in children and adolescents, producing immature osteoids and bones. Previously, amputation of the extremities, concurrent with detection, was the conventional therapy for osteosarcoma and the 5-year survival rate was extremely poor, less than 20%, due to the inability to inhibit pulmonary metastases (1). Recently, the survival rate has increased to 60-80% through the application of combination treatments using surgery and 71 This article is freely accessible online.

Circular RNA circANKIB1 promotes the progression of osteosarcoma by regulating miR-217/PAX3 axis

“…PAX3 has been suggested to play pivotal roles in diverse tumors, including OS [32] , [33] . For example, Fujii et al showed that PAX3 downregulation repressed OS cell growth and induced cell cycle arrest at the G0/G1 phase via modulating p21 expression [17] . Moreover, Zhan et al demonstrated that PAX3 abundance was enhanced in OS tissue specimens, and PAX3 upregulation abated the anti-tumor roles of miR-206 overexpression in OS cells [34] .…”

“…A previous report suggested that miR-217 was lowly expressed in OS tissues and cells, and played a tumor-suppressive role in OS [16] . Besides, paired box 3 (PAX3) has been reported to promote the progression of OS [17] . Through biological analysis, we found that circANKIB1 could specifically bind to miR-217, and miR-217 also had binding sites with PAX3.…”

SLC25A10 performs an oncogenic role in human osteosarcoma

“…P21 is an important cyclin-dependent kinase inhibitor, which suppresses both cell proliferation and metastasis in human osteosarcoma cells. Moreover, overexpression of P21 increases sensitivity of osteosarcoma cells to anti-cancer drugs ( 37 – 39 ). Furthermore, P21 acts as tumor suppressor in human nasopharyngeal carcinoma ( 19 ), cervical cancer ( 20 ), breast cancer ( 40 ), non-small cell lung cancer ( 41 ).…”

Effects of Intestinal Microbial–Elaborated Butyrate on Oncogenic Signaling Pathways

“…P53 binds to p21 promoter to increase p21 expression, causing cell cycle arrest. p21 is also regulated by other transcriptional factors and miRs independent of p53 [162,163]. Thus butyrate can exert an anti-cancer effect through increasing p21 via decreasing miR106B.…”